中文摘要：

目的 同源模建cub8功能域的三维模型,并以计算机辅助的分子对接方法预测cub8功能域与白蛋白的候选结合氨基酸残基.方法 采用insightⅡ工作站对cub8蛋白进行同源模建,对cub8蛋白和白蛋白进行分子对接,寻找白蛋白和cub8的候选结合氨基酸残基.结果 cub8蛋白三维结构为两个反平行的β片层结构,中间以β转角相连.cub8蛋白片段与白蛋白通过正负电势的吸引完成受体与配体的结合.Asp^59-Tyr^60-Leu^61-Glu^62-Leu-Tyr^64和Arg^72-Tyr^73肽段可能是cubilin与白蛋白结合的关键氨基酸残基.结论 利用计算机辅助的分子对接技术,获得cub8和白蛋白相互作用的两个候选结合域,为进一步研究cubilin与白蛋白相互作用奠定基础.

英文摘要：

Objective To build the spatial structure of cub8 functional domain by homologous modeling, and to predict the candidate functional residues of cub8 functional domain binding to albumin by computer-aided molecular decking technique. Methods Molecular modeling of the three-dimensional （3D） structures of cub8 was performed using the homology modules of the software packages Insight Ⅱ 2000. The predicted models were explored to examine the albumin binding affinity and substrate binding pocket. The interaction between cub8 and albmnin was studied with docking program according to the surface electrostatic potential analysis and spatial conformation complement. The stable region structure composed of cub8 and albumin was obtained on the basis of molecular mechanism optimization and molecular dynamics simulation. Results Cub8 was involved in a special structure formed by two layers of antiparallel β sheets connected by β turns. The residues＇ compatibility testing of cub8 with profile-3D method showed that all residues of the modeled structure were compatible. The binding domain between cub8 and albumin was predicted theoretically. Asp^59-Tyr^60-Leu^61-Glu^62-Leu-Tyr^64 and Arg^72-Tyr^73 may be essential for cubilin to bind to albu- min. Conclusion The results lay a theoretical foundation for confirming the active regions of cub8 and designing novel antagonist with computer-guided techniques.